The proposed program project will develop cutaneous gene therapy for junctional epidermolysis bullosa (JEB) while studying key relevant features of cutaneous biology. The goals of this project focus on further characterizing basement membrane zone proteins in relationship to blistering human skin disease, as well as on cutaneous gene regulation strategies, stem cell biology and gene delivery methods. We shall attempt to develop effective approaches for long term delivery of therapeutic genes to the skin as a foundation for gene therapy for JEB and for systematic application in the treatment of human genetic skin disease.